DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Claims 150-153, 155, 156, 158, 166 and 169-173 are pending upon entry of amendment filed on 6/9/26.
Claims 150-153, 155, 156, 158, 166 and 169-173 are under consideration in the instant application.
3. Applicant’s IDS filed on 6/9/26 has been acknowledged.
4. IN light of Applicant’s amendment to the claims filed on 6/9/26 and the terminal disclaimer filed on 6/9/26, the rejections under 35 U.S.C.101, 112 (b), 102 and double patenting rejections (note sections 6-9, 11, 12, 15 and 16 of the office action mailed on 2/9/26) have been withdrawn.
5. The following rejection remains.
6. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
7. Claims 150-153, 155, 156, 158-166 and 169-173 are rejected under 35 U.S.C. 103(a) as being unpatentable over WO2015/042246 (IDS reference, of record) in view of U.S. Pat. 9,220,776 (IDS reference, of record) and U.S.Pub.2005/0276823 (IDS reference, of record) for the reasons set forth in the office action mailed on 2/9/26.
The ‘246 publication teaches administration of LAG-3 and PD-1 antibody in intravenously (p. 7) at 80 mg and 240 mg, respectively. This meets the limitation of ratio of LAG-3 and PD-1 about 1:4 of claim 163. Further, the kits comprising a pharmaceutical composition comprising LAG-3 and PD-1 (p.8, 17) with pharmaceutically acceptable excipients are taught. The antibody includes claimed SEQ ID NO:3, 5, 19 and 21 where BMS986010 and BMS-936558 comprise the claimed SEQ ID NO:1-3, 5, 9 and 21, respectively. Further it is evidenced to comprises the CDR’s set forth in CDRs in SEQ ID NO: 1-12, 23-28, respectively as in claims 153 and 161 of the instant application.
Further, the 246 publication teaches kits and dosage forms in pre-filled syringes as well as infusion bags required by the appropriate vehicles and administration methods (p. 17).
The disclosure of the ‘246 publication differs from the instant claimed invention in that it does not teach the use 5-50mM of buffer (note examples in claim 154, e.g. histidine), 50-300mM of stabilizer (note examples 154, e.g. sucrose), 0.001-1% of surfactant, 5uM to 1mM of chelating agent or DTPA, and pH of 5-6 as in claims 150, 154-158 of the instant application.
The ‘776 patent teaches formulation of PD-1 antibody in the presence of 10-20mM histidine buffer, 70mg/ml of sucrose (7%, with the molecular weight of 342, equivalent of 205mM), 0.02-0.05% polysorbate with USP water at pH about 5.5 (col. 19-20, claims 1-6). The pH about 5.5 reads on the claimed about 5.8. The ‘776 patent allows addition of 0.9% sodium chloride and sterile dextrose for infusion (col. 19). The PD-1 antibody is stabilized in the formulation comprising histidine, sucrose, polysorbate and/or NaCl or dextrose in lyophilized formulation (col. 10-25). The antibody composition improves stability by reduction of aggregation (col 15).
The ‘823 publication teaches addition of DTPA from 1uM-10mM in the presence of histidine from 10uM-200mM with isotonic agent including sucrose upto 25% ([0059-0073]). The addition of DTPA improve stability by reduction of oxidative degradation as DTPA acts as metal chelators/
It would have been obvious to one of ordinary skill in the art at the time the invention was made to utilize histidine, DTPA, sucrose and polysorbate as taught by the ‘776 patent and ‘823 publication into the LAG-3 and PD-1 antibody formulation taught by the ‘246 publication.
One of ordinary skill in the art at the time the invention was made would have been motivated to do so because the formulation of PD-1 and LAG-3 antibody in the histidine, sucrose, polysorbate and DTPA of known concentration would stabilize and improve shelf life by reduction of aggregation caused by the oxidative degradation of antibody. The composition that is suitable for PD-1 antibody of the ‘776 patent would be suitable for PD-1 and LAG-3 as the ‘246 publication discloses co-formulation of those two antibodies and the DTPA is suitable for any antibody (p. 2-5) where the addition of antioxidant is generally known for antibody formulation art.
From the teachings of references, it would have been obvious to one of ordinary skill in art to combine the teachings of the references and there would have been a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of the ordinary in the art at the time of invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Applicant’s response filed on 6/9/26 has been fully considered but they were not persuasive.
Applicant has asserted that the concentration of histidine in the ‘776 patent is limited to 10mM while the currently amended claims recite 20mM of histidine. In addition, Applicant has asserted that the formulation of antibody for specific antibody is unpredictable and aggregation depends on CDRs of antibody. Further, it is an empirical exercise to formulate the specific antibody and it is unpredictable to formulate PD-1 and LAG-3 antibodies together based on the Remarks for 14/008,604 that is allowed.
However, unlike Applicant’s assertion, the ‘246 publication allows PD-1 and LAG-3 antibody in the same formulation (p.16) in the pharmaceutical composition. IN addition, the ‘776 patent teaches PD-1 antibody formulation in the presence of 10mM of histidine, about 250mM of sucrose and 0.02% of polysorbate at pH 5-6. Applicant is reminded that the ‘776 patent issued from USSN 14/008604 does not use chelating agent. As taught by the ‘823 publication, histidine buffer concentration is increased to 200mM upon addition of chelating agent (see claims, p. 14).
Moreover, the ‘823 publication does not limit to any specific antibody (note claims).
As such, although the ‘776 patent focuses on 10mM of histidine, there is motivation to increase sucrose and/or histidine concentrations upon addition of chelating agent based on the ‘823 publication. Applicant is reminded that obviousness does not require absolute predictability and one cannot show nonobviousness by attacking references individually where the rejection is based on the combination of the references. See MPEP 2143.02 and 2145.
8. The following new ground of rejection is necessitated by Applicants’ amendment filed on 6/9/26.
9. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
10. Claims 150-153, 155, 156, 158-166 and 169-173are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a New Matter rejection.
The specification or the original claims as filed does not provide a written description the phrases “1-300mg of LAG-3 antibody, 20mM of histidine buffer, about 250mM of sucrose and about 0.05% of polysorbate at pH 5-6.5.” Applicants assert that the currently added limitation is found from the [0004, 0023 or 0127] of the specification. The specification supports for 20mM of histidine, about 250mM sucrose and 0.05% polysorbate in the presence of 20uM to about 50uM of DPTA or EDTA at most. However, the specification does not support for the limitations in the absence of chelating agent as currently amended.
The currently amended range is not supported by the original claims or instant specification.
The instant claims now recite a limitation which was not clearly disclosed in the specification as filed, and now changes the scope of instant disclosure as filed.
Such limitations recited in the present claims, which did not appear in the specification as filed, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C.112.
11. No claims are allowable.
12. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to YUNSOO KIM whose telephone number is (571)272-3176. The examiner can normally be reached Mon-Fri 8:30-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Yunsoo Kim
Patent Examiner
Technology Center 1600
August 4, 2026
/YUNSOO KIM/Primary Examiner, Art Unit 1641
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